Chemotherapy for some cancer patients can be worse than the disease itself. In some cases the tumor may mutate and stop responding to the drug or the patient might not respond to the treatment.
But University of California, Los Angeles (UCLA) researchers have developed a non-invasive approach that could one day allow doctors to predict a tumor's response to a drug before prescribing therapy. This in turn could help physicians to quickly pinpoint the most effective treatment and personalize it to the patient's biochemistry.
During the study, the group injected a probe into mice that had developed leukemia and lymphoma tumors. According to the study results, after an hour, the researchers imaged the animals' bodies with positron emission tomography (PET), a non-invasive scan often used on cancer patients to identify whether a tumor has spread from its original site or returned remission.
PET is a nuclear medicine imaging modality which produces a 3-D image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Images of tracer concentration in 3-D space within the body are then reconstructed by computer analysis.
In modern scanners, this reconstruction is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.
Dr. Caius Radu, a researcher at the Crump Institute for Molecular Imaging and assistant professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, said that the approach is actually a probe that can be injected into a living organism.
"Unfortunately many of these chemotherapy procedures have serious side effects and are very risky for patients," he said.
"For the first time, we can watch a chemotherapy drug working inside the living body in real time," Radu said. "We plan to test this method in healthy volunteers within the year to determine whether we can replicate our current results in humans."
Here's how it works:
"The PET scanner operates like a molecular camera, enabling us to watch biological processes in living animals and people," Radu told Medical Device Daily. "Because we tag the probe with positron-emitting particles, the cells that absorb it glow brighter under the PET scan. The probes are injected in mice and in low doses so there is no toxicity in patients."
According to the study, once the probe is inserted, a PET scan can then offer a preview for how the tumor will react to a specific therapy.
Radu's group said it believes tumor cells that absorb the probe will also take up the drug. If the cells do not absorb the probe, it suggests that the tumor might respond better to another medication.
In an earlier study, Radu and his colleagues created a small probe by slightly altering the molecular structure of gemcitabine, one of the most commonly used chemotherapy drugs. They labeled the probe with a special tag that enabled them to watch its movement throughout the body during imaging.
In the future, the UCLA researchers said they plan to add more layers to the scope of their research by examining whether or not the probe can predict cellular response to several other chemotherapy drugs. A goal for the group is to see whether the probe can provide a diagnostic test of clinical value.
If testing in healthy subjects proves safe and effective, the researchers will begin recruiting volunteers for a larger clinical study of the probe in cancer patients.
Radu added that in the future the group would look at a bunch of cancers such as lymphomas, in which the probe can be used.
"I hope that by the end of the year we will be able to see if the probe works in humans," he said. "The beauty of this approach is that it is completely non-invasive and without side effects."
The study was funded by the Dana Foundation (New York), National Cancer Institute (Bethesda, Maryland), Department of Energy (Washington), and Howard Hughes Medical Institute (Chevy Chase, Maryland).